SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Dovonex® Ointment

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gram of ointment contains 50 micrograms of calcipotriol.

For excipients, see section 6.1

3    PHARMACEUTICAL FORM

Ointment.

Off white to yellowish white translucent ointment.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Dovonex Ointment is indicated for the topical treatment of plaque psoriasis (psoriasis vulgaris) amenable to topical therapy.

4.2. Posology and Method of Administration

Adults:    Dovonex Ointment should be applied to the affected area once or

twice daily. For maximum benefit use the ointment twice daily. Maximum weekly dose should not exceed 100g.

Children over 12 years: Dovonex Ointment should be applied to the affected area twice

daily. Maximum weekly dose should not exceed 75g.

Dovonex Ointment should be applied to the affected area twice daily. Maximum weekly dose should not exceed 50g.

Children under 6 years: There is limited experience of the use of Dovonex Ointment in

These dose recommendations are based on extensive experience in adults. In respect of children, clinical experience in children has shown Dovonex to be safe and effective over eight weeks at a mean dose of 15g per week but with wide variability in dose among patients. Individual dose requirement depends on the extent of psoriasis but should not exceed the above recommendations. There is no experience of use of Dovonex in combination with other therapies in children.

4.3 Contraindications

Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

Due to the content of calcipotriol, Dovonex® is contraindicated in patients with known disorders of calcium metabolism (see section 4.4).

4.4 Special warnings and precautions for use

Effects on calcium metabolism

Due to the content of calcipotriol, hypercalcaemia may occur if the maximum weekly dose is exceeded. Care should be exercised in patients with other types of psoriasis, since hypercalcaemia has been reported in patients with generalised pustular or erythrodermic exfoliative psoriasis. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the dosage recommendations are followed. The maximum weekly dose in adults is 100 g of cream or ointment (equivalent to 5 mg of calcipotriol) or 60 ml of scalp solution (equivalent to 3 mg of calcipotriol). When cream, ointment or cutaneous solution are applied together, the total dose of calcipotriol should not exceed 5 mg per week.

Local adverse reactions

Dovonex® should not be used on the face, as it may cause skin irritation.

The patient must be instructed in correct use of the product to avoid accidental transfer to the face and eyes. Hands must be washed after each application to avoid accidental transfer to these areas.

UV exposure

During Dovonex^® Ointment treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Dovonex^® should be used with UV radiation only if the physician and patient consider that the potential benefits outweigh the potential risks (see section 5.3).

Unevaluated use

Due to lack of data, Dovonex® should be avoided in guttate, erythrodermic, exfoliative and pustular psoriasis.

Due to lack of data, Dovonex® should be avoided in patients with severe liver and kidney disease.

Adverse reactions to excipients

Dovonex^® ointment contains propylene glycol as an excipient which may cause skin irritation.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with Dovonex^®.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of the use of topical calcipotriol during human pregnancy has not been established, however studies in animals have shown reproductive toxicity when calcipotriol was administered orally. Calcipotriol should not be used during pregnancy unless clearly necessary.

Breast-feeding

It is unknown whether calcipotriol is excreted in breast milk. Caution should be exercised when prescribing Dovonex® to women who breast-feed. The patient should be instructed not to use Dovonex® on the breast when breast-feeding.

Fertility

Studies in rats with oral doses of calcipotriol demonstrated no impairment of male and female fertility.

4.7 Effects on ability to drive and use machines

Calcipotriol has no or negligible influence on the ability to drive and to use machines.

4.8 Undesirable effects

The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies and spontaneous reporting.

The most frequently reported adverse reactions during treatment are pruritus, skin irritation and erythema.

Systemic reactions (hypercalcaemia and hypercalciuria) have been reported. The risk of developing such reactions increases if the recommended total dose is exceeded (see section 4.4).

Adverse reactions are listed by MedDRA SOC and the individual adverse reactions are listed starting with the most frequently reported. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

>1/10

>1/100 to <1/10 >1/1,000 to <1/100 >1/10,000 to <1/1,000 <1/10,000

Rare (>1/10,000 to <1/1,000)	Hypercalciuria
General disorders and administration site conditions
Common (>1/100 to <1/10)	Application site pain
Uncommon (>1/1,000 to <1/100)	Application site pigmentation changes

* Various types of rash reactions such as rash erythematous, rash maculo-papular, rash morbilliform, rash papular and rash pustular have been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Use above the recommended dose may cause elevated serum calcium which quickly subsides when treatment is discontinued.

The symptoms of hypercalcaemia include polyuria, constipation, muscle weakness, confusion and coma.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: D05A X02.

Pharmacotherapeutic group: Antipsoriatics for topical use.

Calcipotriol is a vitamin D derivative. In vitro data suggest that calcipotriol induces differentiation and suppresses proliferation of keratinocytes. This effect is the proposed basis for its effect in psoriasis.

5.2. Pharmacokinetic Properties

Data from a single study containing 5 evaluable patients with psoriasis treated with 0.3 - 1.7g of a 50 micrograms/g tritium labelled calcipotriol ointment suggested that less than 1% of the dose was absorbed.

However, total recovery of the tritium label over a 96 hour period ranged from 6.7 to only 32.6%, figures maximised by uncorrected chemiluminescence. There were no data on tissue distribution or excretion from the lungs.

5.3 Preclinical safety data

The effect on calcium metabolism is approximately 100 times less than that of the hormonally active form of vitamin D3.

Calcipotriol has shown maternal and foetal toxicity in rats and rabbits when given by the oral route at doses of 54 pg/kg/day and 12 pg/kg/day, respectively. The foetal abnormalities observed with concomitant maternal toxicity included signs indicative of skeletal immaturity (incomplete ossification of the pubic bones and forelimb phalanges, and enlarged fontanelles) and an increased incidence of supernumerary ribs.

There is insufficient pharmacokinetic data available to quantify the safety margin for the embryofoetal effects.

A dermal carcinogenicity study in mice and an oral carcinogenicity study in rats revealed no special hazard to humans.

In a study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and dermally administered calcipotriol for 40 weeks at dose levels corresponding to 9, 30 and 90 pg/m /day (equivalent to 0.25, 0.84, 2.5 times the maximum recommended daily dose for a 60 kg adult, respectively), a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UV radiation to induce skin tumours. The clinical relevance of these findings is unknown.

6. PHARMACEUTICAL PARTICULARS

6.1. List of Excipients

Disodium edetate, disodium phosphate dihydrate, DL-a-tocopherol, liquid paraffin, macrogol(2)stearyl ether, propylene glycol, purified water and white soft paraffin.

6.2 Incompatibilities

Should not be mixed with other medicinal products.

6.3 Shelf life

Unopened container: 2 years.

After first opening of container: 6 months.

6.4. Special Precautions for Storage

Do not store above 25 °C

6.5 Nature and contents of container

Lacquered aluminium tube with polypropylene screw cap. Pack sizes: 30g, 60g, 100g and 120g.

Sample packs of 5g and 15g.

Polyethylene-aluminium laminate tube with screw cap. Pack size:    240g.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

LEO Laboratories Limited

Horizon

Honey Lane

Hurley

Maidenhead

Berkshire

SL6 6RJ

UK

8. MARKETING AUTHORISATION NUMBER

PL 0043/0177

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

10 January 1991

10 DATE OF REVISION OF THE TEXT

13/02/2015